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On the Structure and Gating Mechanism of the Mitochondrial Channel, VDAC

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Abstract

There is considerable evidence that the voltage-gated mitochondrial channel VDAC forms a β-barrel pore. Inferences about the number and tilt of β-strands can be drawn from comparisons with bacterial β-barrel pores whose structures have been determined by x-ray crystallography. A structural model for VDAC is proposed (based on sequence analysis and electron crystallography) in which the open state is like that of bacterial porins with several important differences. Because VDAC does not occur as close-packed trimers, there are probably fewer interpore contacts than in the bacterial porins. VDAC also appears to lack a large, fixed intraluminal segment and may not have as extensive a region of uniformly 35°-tilted β-strands as do the bacterial porins. These structural differences would be expected to render VDAC's β-barrel less stable than its bacterial counterparts, making major conformational changes like those associated with gating more energetically feasible. A possible gating mechanism is suggested in which movement of the N-terminal α-helix out of the lumen wall triggers larger-scale structural changes.

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Authors and Affiliations

  1. Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, Albany, New York, 12201–0509

    Carmen A. Mannella

  2. Department of Biomedical Sciences, School of Public Health, University at Albany (SUNY), Albany, New York

    Carmen A. Mannella

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  1. Carmen A. Mannella
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Mannella, C.A. On the Structure and Gating Mechanism of the Mitochondrial Channel, VDAC. J Bioenerg Biomembr 29, 525–531 (1997). https://doi.org/10.1023/A:1022489832594

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  • DOI: https://doi.org/10.1023/A:1022489832594

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